In order to explore the linkage between the genetic disturbance and phenotypic expression of human myelogenous leukemia, variant cultures of HL-60 cells have been developed and cloned. These variants were chosen on one or more of the following bases: (1) selectability in tissue culture for utilization in cloning and somatic cell hybrid techniques, (2) possible association with specific chromosomal gene loci which might be quantitatively measurable, and (3) probable effect on specific differentiation and/or replicative properties of the leukemic cells. Variants resistant to 5-bromo-2-deoxyuridine, 6-thioguanine, dimethylsulfoxide, retinoic acid and oubain have been developed. Measurable differences have been demonstrated in growth characteristics in suspension and viscous culture media, in responsiveness to specific differentiation inducers, in enzymatic composition in cytogenetic constitution, and in surface membrane biochemistry.